Real-world outcomes of brentuximab vedotin maintenance after autologous stem cell transplant in relapsed/refractory classical Hodgkin lymphoma: Is less enough?
Authors: Charlotte Burton Wagner, Daniel Arthur Ermann, Kenneth M. Boucher, Adrienne Nedved, Ivana N. M. Micallef, Haris Hatic, Gaurav Goyal, Erin Hickey, Amanda Fegley, Courtney Samuels, Manali K. Kamdar, Sheeba Habeeb Ba Aqeel, Pallawi Torka, Kira MacDougall, Azra Borogovac, Sridevi Rajeeve, Kalub Fedak, Elizabeth Travers, Harsh Shah
Journal: Journal of Clinical Oncology (2022)

7514 Background: The AETHERA trial demonstrated improvement in PFS with 16 cycles of brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in BV-naive patients with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, in real world, patients are rarely able to complete all 16 cycles of BV at full dose. We performed a multicenter retrospective study to assess the impact of cumulative dose on toxicity and 2-year PFS. Methods: Patients from 11 institutions across the US who had received at least one cycle of BV maintenance after ASCT for r/r cHL with one of these features were included: primary refractory disease (PRD), extra-nodal disease (END), or relapse &lt; 12 months of diagnosis (RL&lt;12). PFS was compared between the three cohorts based on a total cumulative dose of 28.8 mg/kg (1.8 mg/kg x 16 cycles): C1, those that received &gt;75% (21.7 to 28.8 mg/kg) cumulative dose of BV, C2, those that received between 51% -75% (14.5 to 21.6 mg/kg) dose and C3, those that received ≤ 50% (≤ 14.4 mg/kg) dose. Results: Between July 2015-June 2019, 100 patients with a median age of 34 years (19-70) underwent ASCT for r/r cHL. At relapse, 44% had PRD, 47% had RL&lt;12, 39% had END and 45% had received BV as initial (1%) or salvage (44%) therapy. 71% had CR before ASCT and 23% received &gt;1 line of salvage (&gt;1 SLT). There was no difference in baseline characteristics between the cohorts. Thirty-six patients were in C1, 27 in C2, and 37 in C3. Only 14% of patients received full cumulative dose of BV. The median number of cycles completed was 12. Fifty-seven patients discontinued early: 39 for toxicity, 7 for progression, 5 for patient preference, 2 for cost and 4 for other reasons. Six of the patients who stopped early for progression were in C3. Grade ≥3 adverse events for neuropathy, neutropenia, and infections were 16%, 7%, and 5% respectively. There was no difference in severity of neuropathy in patients who had received BV prior to ASCT (p=.37). The median follow up was 3.37 years (.4–6.35). The 2-year PFS was 85% for all subjects, 94% for C1, 84% for C2, and 72% for C3 (p=.079) (Table). Patients in C3 had worse PFS compared to C1 (p=.035); this difference remained significant after adjusting for five other factors. There was no difference in PFS between C1 and C2 (p=.29). Conclusions: The majority of patients discontinued BV maintenance early due to toxicity. 2-year PFS was robust regardless of cumulative dose of BV. We conclude that total cumulative dose of 28.8 mg/kg of BV maintenance is not necessary and 51%-75% of total BV dose may still attain a similar PFS advantage. [Table: see text]